HLA, infections and inflammation in early stages of atherosclerosis in children with type 1 diabetes

Acta Diabetol. 2018 Jan;55(1):41-47. doi: 10.1007/s00592-017-1063-1. Epub 2017 Oct 24.

Abstract

Aims: This prospective study focuses on risk factors for arterial damage in children with type 1 diabetes (T1D).

Methods: Eighty children and adolescents with T1D were investigated twice, approximately 2 years apart, for carotid artery intima-media thickness (cIMT) and compliance (CAC), flow-mediated dilatation (FMD) of the brachial artery, and plasma levels of matrix metalloproteinase (MMP)-8. All subjects were genotyped for HLA. The number of respiratory tract infections (RTI) during the past year was obtained by a questionnaire in 56 patients.

Results: cIMT progression, defined as percentage (%) change of cIMT from baseline, correlated inversely with the % changes of both CAC (p = 0.04, r = - 0.3; n = 62) and FMD (p = 0.03, r = - 0.3; n = 47). In multivariate analysis, RTI frequency correlated significantly with cIMT progression irrespective of age, diabetes duration, BMI, and HbA1c (p = 0.03, r = 0.3). When patients were divided in relation to RTI, the association of DQ2/8 with cIMT progression remained significant in patients with over three infections/year (p = 0.04, r = 0.3). During follow-up, the group of DQ2/8 patients with hsCRP > 1 mg/l showed significantly higher levels of plasma MMP-8 than the non-DQ2/8 group.

Conclusions: The diabetes-risk genotype DQ2/8 and systemic inflammation contribute to pro-atherosclerotic vascular changes in children and adolescents with T1D.

Keywords: Children; Infections; Intima-media thickness; Matrix metalloproteinase-8; Type 1 diabetes.

MeSH terms

  • Adolescent
  • Adult
  • Atherosclerosis / complications
  • Atherosclerosis / epidemiology*
  • Atherosclerosis / genetics
  • Atherosclerosis / physiopathology
  • Brachial Artery / physiopathology
  • Carotid Intima-Media Thickness
  • Child
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / epidemiology*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / physiopathology
  • Disease Progression
  • Female
  • HLA-DQ Antigens / genetics*
  • Humans
  • Infections / complications
  • Infections / epidemiology*
  • Infections / genetics
  • Infections / physiopathology
  • Inflammation / complications
  • Inflammation / epidemiology*
  • Inflammation / genetics
  • Inflammation / physiopathology
  • Male
  • Matrix Metalloproteinase 8 / blood
  • Risk Factors
  • Young Adult

Substances

  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • HLA-DQ8 antigen
  • MMP8 protein, human
  • Matrix Metalloproteinase 8